Encapsulation of Cryptococcus neoformans with glucuronoxylomannan inhibits the antigen-presenting capacity of monocytes.
This report examines the effect of the major capsular polysaccharide of Cryptococcus neoformans, glucuronoxylomannan (GXM), on the antigen-presenting capability of human monocytes treated with acapsular cells of C. neoformans. We found that pretreatment of acapsular cryptococci with GXM downregulates, in a dose-dependent manner, the antigen-presenting capacity of monocytes, leading to reduced proliferative T-lymphocyte responses. Similar levels of suppression occurred when monocytes were exposed to encapsulated cryptococci or acapsular cryptococci that were pretreated with GXM. The magnitude of the T-cell response correlated with the ability of monocytes to ingest the yeast. Supernatant fluids from cocultures of monocytes and T cells cultured with encapsulated cryptococci contained higher levels of interleukin-10 (IL-10) than supernatant fluids of cells with acapsular cryptococci. Addition of anti-IL-10 monoclonal antibodies to the incubation medium of monocytes and T cells cultured with encapsulated cryptococci restored proliferative T-cell responses to levels observed during culture with acapsular cryptococci. Finally, treatment of monocytes with encapsulated cryptococci or GXM-treated acapsular cryptococci suppressed expression of class II major histocompatibility complex (MHC) molecules in a manner consistent with previous reports of IL-10-mediated suppression of class II MHC molecules and suppression of proliferative T-cell responses. These results suggest a link between GXM encapsulation, increased IL-10 synthesis by monocytes, decreased expression of class II MHC molecules on monocytes, and reduced proliferative T-cell responses.
Retini
C
C
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Vecchiarelli
A
A
Monari
C
C
Bistoni
F
F
Kozel
T R
TR
D017951:Antigen Presentation; D003455:Cryptococcus neoformans / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology*; D011134:Polysaccharides / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D011134:Polysaccharides; D016753:Interleukin-10; C027478:glucuronoxylomannan